Despitethe long-termpromise of stem-cell and otherbiological approaches, currentoptionsto improve function following spinal cord injury (SCI) remain quite limited. However, brain machine interfaces (BMIs) that use cortical activity to drive functional electrical stimulation (FES) of muscles or the spinal cord have great promise not only for the restoration of motor ability when using the BMI, but also for improved functional rehabilitationsothattheirperformanceisimprovedwhentheBMIisremoved.Theoverallgoalofourresearch istoidentifystrategiesthatmaximizebothofthesepotentialstrengthsofcortically-controlledFES. Asystemusingcorticalactivitytodrivestimulationofindividualmusclesmightmaximizetherestoration ofmotorfunction:byenablinguserstovarytheamplitudeandtimingofindividualmuscles,movementscan potentiallybeadaptedasnecessarytoachievetaskdemands.Alternatestrategiesofproducingmovement, suchasactivationofmusclegroupsorofsitesinthespinalcordproducinglimbflexionorextension,will reducetherangeofpossiblemovements.AlthoughthesestrategiesmightbesimplertolearnafterSCIthan controlofindividualmuscles,theyclearlylimitthelevelofmotorfunctionthatcanberestored. Inordertoachievethegreatestfunctionalrehabilitation,however,spinalstimulationmightbeamore promisingstrategythanmusclestimulation.Repeatedspinalstimulationmightmaintainthefunctionofspinal pathwaysinvolvedintheproductionofmovementandenablerestorationofconnectionsfromdescending systemsthroughassociativeplasticity.Conversely,sincemusclestimulationdoesnotactivatespinalpathways toproducemovement,itmightproducelessfunctionalrehabilitation. Thereisthereforeapotentialtradeoffbetweenmuscleandspinalstimulation:musclestimulationenables high levels of motor ability but might limit functional rehabilitation, while spinal stimulation might enhance rehabilitation but limit flexibility. Our research will investigate this tradeoff, with the goal of designing a hybrid system that combines spinaland muscle stimulation toachievehigh levels of both motor ability and functional rehabilitation. We will perform these experiments in rats, implanting electrodes in the cortex to record neural activity and in the spinal cord and muscles to produce movements. We will then train rats to use these systems after SCI,evaluating whether they can improve motorabilityand functional rehabilitation. In Aim1, wewill evaluate whetheranimalscanproducehighlevelsofmotorabilitywithasystemusingcorticalactivitytocontrolactivation of individual muscles. In Aim 2, we will evaluate whether animals using cortical activity to control activation of spinalstimulationhavebetterfunctionalrehabilitation.Finally,inAim3wewillevaluatewhetherahybridsystem that controls activation of both muscle and spinal stimulation, exploits the advantages of each approach to producemovement,resultinginhighlevelsofbothmotorabilityandoffunctionalrehabilitation.